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标题：An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model
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作者：Keita Yamauchi ; Shoji Yasunaga ; Hiromu Kawasaki 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2003
卷号：26
期号：2
页码：210-215
DOI：10.1248/bpb.26.210
出版社：The Pharmaceutical Society of Japan
摘要：The usefulness of kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating effect (DADE) of lipo-PGE₁ (a lipid emulsion preparation of prostaglandin E₁ for injection) preparations. Lipo-PGE₁ was administered intravenously via the umbilical vein by a bolus injection or an infusion in newborn rats 60 min after the delivery. The DADE data were expressed as the inner diameter ratio between the ductus arteriosus and the main pulmonary artery, and were analyzed by a pharmacological response kinetic (PRK) model consisting of an E _max model and a simple pharmacokinetic model as the pharmacodynamic- and the pharmacokinetic-component, respectively. The latter component includes the release process of free-PGE₁ from the lipid phase of lipo-PGE₁, followed by distribution to the effect compartment. The E _max value was estimated by the maximal DADE observed 10 min after the bolus administration of each dose, and the value was fixed in the PRK analysis. The regression curves given by simultaneous non-linear least squares regression analysis were satisfactorily fitted to the observed DADE data at all doses. Prediction of the DADE of lipo-PGE₁ in an infusion study was satisfactorily done using the estimated parameters in the i.v.-study. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response-time data is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in predicting the time courses of the drug's pharmacological response in different dosage regimens.
关键词：lipo-prostaglandin E1;ductus-arteriosus;pharmacokinetic/pharmacodynamic model;pharmacological response kinetic model;newborn rat;targeting-type drug